Objectives: The aim of the proposed research is to assess alveolar capillary permeability in immature animals. This will be done in three ways: 1) Endothelial permeability will be estimated in intact piglets and puppies by comparing the extraction ratios of diffusible and nondiffusible indicators on the upslope of first-circulation time- concentration curves. Appropriate indicators are injected intravenously as a bolus, and arterial blood is sampled serially and analyzed for indicator concentrations. 2) Alveolar-capillary permeability will be estimated in the isolated, perfused, fluid-filled, immature lung. The rate of escape of various ions and molecules from the vascular compartment is measured by serial sampling of the perfusate. 3) Endothelial permeability is estimated from determinations of reflection coefficients of various substances added to the vascular perfusate. The isolated, perfused, mechanically ventilated lung is suspended on a balance and the osmotic activity of known quantities of added solute is determined gravimetrically. The proposed studies are relevant to clinical situations in which there is abnormal leakage of fluid and protein from lung capillaries, for example, hyaline membrane disease.